Project: Preventing Alzheimer's disease conversion by monitored vibration treatment

Acronym	Good Vibes (Reference Number: JPND2022-120)
Project Topic	Alzheimer’s disease (AD) is a frequent neurodegenerative disease associated with massive healthcare costs across the globe, not the least because of an aging population combined with lack of effective treatments. AD is characterized by slow accumulation of abnormal protein, e.g., β-amyloid in parenchymal brain tissue and arterial walls, with a strong link to several vascular risk factors. Recent studies suggest that a failure of glymphatic brain solute transport linked to neurovascular defects contributes to AD. Our collaborative findings with advanced micro- and macroscopic neuroimaging have directed our focus towards mechanisms that can prevent AD by augmenting the pulsatile perivascular cerebrospinal fluid (CSF) solute efflux from the brain. Our consortium has pioneering results in improving tracer efflux from perivascular space using a novel electroacoustic (EAC, c.f. Fig. 1) vibration treatment and removal of β-amyloid plaques with focused ultrasound (FUS), a treatment that can restore memory in mice. The major aim of this proposal is to understand how physical oscillations can be used to improve glymphatic hydrodynamics and waste efflux. We have previously developed wearable multimodal monitoring of brain pulsations pertaining to the brain solute transport. We intend to verify the efficiency of the EAC & FUS augmentation of solute efflux using a combined wearable direct-current electroencephalography (dcEEG) with water targeted near-infrared spectroscopy (wNIRS) providing readouts for brain water hydrodynamic parameters such as transvection, blood-brain barrier (BBB) permeability and tissue elasticity. The wearable measurements and treatment responses will be validated against gold standard tools of measuring CSF solute transport; multiphoton microscopy in mice, light sheet microscopy, SPECT, MREG in pigs, and ultrafast MREG & TCD brain scans in humans combined with multinational clinical datasets from this consortium. In summary, our original preliminary data, established collaborations and synergies in the proposed consortium, access to unique patient cohorts, our mechanistic know-how, and clinical experience in brain clearance gives us a competitive advantage for developing targeted and monitored treatment to enhance CSF driven brain clearance and to prevent AD conversion due to protein waste accumulation.
Network	JPND
Call	Understanding the mechanisms of non-pharmacological interventions

Project partner

Number	Name	Role	Country
1	University of Oulu	Coordinator	Finland
2	University Hospital of Copenhagen	Partner	Denmark
3	Radboud University	Partner	Netherlands
4	Semmelweis University	Partner	Hungary
5	University of Copenhagen	Partner	Denmark